There is a need for development of implantable sensors for continuous monitoring of glucose in diabetes. We have developed an implantable glucose sensor based on immobilized glucose oxidase coupled to an oxygen electrode and have operated the sensor as an intravenous implant for over 100 days in dogs. Our glucose sensor currently holds the world's record for continuous, long-term operation as a functioning implant without recalibration. We were also the first to develop and use implantable telemetry and instrumentation with implanted glucose and oxygen sensors. These achievements demonstrate the feasibility of continuous, long-term sensing of glucose employing implanted instrumentation and telemetry in animals but it is necessary to develop a small instrumentation package for eventual human use. The package would include low-current input amplifiers or potentiostats capable of operating the sensors, coupled to telemetry transmission or data storage and retrieval devices. For long-term applications, implantable instrumentation with telemetry must be packaged in hermetically sealed containers. Prototype versions of these integrated devices must be built and tested before more costly large-scale integrated fabrication is justified. In this revised Phase I project we plan to (1) develop complete system and component functional specifications to serve as a basis for circuit design; (2) design, build and test a first generation benchtop version of the system; (3) design, build and test a second generation "wearable" version of the system; and (4) develop a first generation integrated circuit chip schematic and complete a first round of circuit performance simulations. These studies will prepare the way for chip fabrication, integration with the sensor, and extensive implantation studies in animals to be carried out in Phase II. PROPOSED COMMERCIAL APPLICATION: The management of diabetes consumes 15% of total national health care expenditures, 25% of MediCare expenditures, and is responsible for an enormous, untold cost in human resources. These costs could be reduced substantially by better blood glucose control resulting from improved insulin replacement, made possible by continuous monitoring of blood glucose. The instrumentation and telemetry package to be designed here is essential for sensor implementation. There are several million people with diabetes who could benefit.